Daniel A. Gold

Cognitive impairment and Alzheimer disease and related dementias are increasingly prevalent and carry significant morbidity. Growing evidence has highlighted the complex interactions between cardiovascular and brain health, implicating vascular dysfunction in the pathogenesis of many forms of cognitive impairment. The American Heart Association (AHA) and the American Stroke Association have outlined a comprehensive framework, known as Life's Essential 8, that includes 4 behavioral health factors (healthy dietary pattern, physical activity, avoidance of nicotine, and healthy sleep) and 4 health factors (cholesterol, blood glucose, blood pressure, body mass index) that collectively define optimum cardiovascular health. Modifiable risk factors account for an estimated 40% of worldwide dementia. Adherence to Life's Essential 8 principles may also help individuals mitigate the risk of cognitive impairment via improved cardiovascular health. However, a comprehensive understanding of the causal relationships between vascular and behavioral risk factors and Alzheimer disease and related dementias remains unclear and requires further study. This narrative review summarizes well‐established data and highlights new data for how health and behavioral factors included in Life's Essential 8 also promote optimal brain and cognitive health.

The management of a chronic total occlusion (CTO) of a coronary artery has been a conundrum in interventional cardiology, as revascularization has not been proven to provide a mortality benefit. However, there are subgroups of patients with a CTO that have high levels of ischemia on myocardial perfusion imaging and high circulating levels of high sensitivity troponin‐I (hsTn‐I) and N terminal pro‐brain natriuretic peptide (NT pro‐BNP) that are at a particularly high‐risk for adverse cardiovascular events. These high‐risk subgroups of patients with a CTO may have not been well represented in prior clinical trials, and may gain a mortality benefit from revascularization of the CTO. Conversely, patients with low levels of ischemia and these biomarkers are at lower risk and may not gain a mortality benefit from revascularization of their CTO. It is important for future randomized controlled trials to investigate the efficacy of CTO PCI in patients with elevated biomarkers and high ischemic burden on myocardial perfusion imaging to determine if patients at high‐risk gain a mortality benefit from revascularization.

Background: Chest pain (CP) in patients with nonobstructive coronary artery disease is a therapeutic challenge affecting morbidity and mortality. We aimed to identify clinical factors associated with CP in this population, hypothesizing that obesity and depressive symptoms are associated with CP. Methods and Results: In 814 patients with angiographically confirmed nonobstructive coronary artery disease, we measured sociodemographic variables, clinical risk factors, medications, and Patient Health Questionnaire 9 scores for depressive symptoms. We assessed CP frequency and prevalence by using all items from the Seattle Angina Questionnaire angina frequency domain to generate an angina frequency composite score. In the overall sample (58.8±11.7 years old, 52.6% female), 42.8% had obesity, and 71.5% had CP, with an angina frequency composite score (SD) score of 76.4 (22.1). Compared with individuals without obesity, individuals with obesity had a higher prevalence (77.6% versus 67%, P P =0.02). Obesity was independently associated with CP occurrence (odds ratio [OR], 1.7 [95% CI, 1–2.9], P =0.04). Obesity's connection with CP was only in men: men with obesity had more frequent CP (angina frequency composite score, 75.8 [SD, 20.1] versus 82.1 [SD, 19.9], P =0.002) and more prevalent CP (79.5% versus 58.2%, P P =0.03) was independently associated with CP and partly mediated the association between obesity and CP. Conclusions: Obesity and depressive symptoms were independently associated with CP in individuals with nonobstructive coronary artery disease, particularly in men, and depressive symptoms partly mediated this association.

Background: Literature suggests a bidirectional association between advanced hepatic fibrosis (AHF) and coronary artery disease (CAD). We evaluated the association of AHF with immune activation, systemic inflammation, and adverse outcomes in patients with CAD. Methods and Results: A fibrosis‐4 index cutoff value ≥2.67 was used to define AHF. Circulating levels of soluble urokinase plasminogen activator receptor and hsCRP (high‐sensitivity C‐reactive protein) were measured as markers for immune activation and systemic inflammation, respectively. The relationship of AHF with soluble urokinase plasminogen activator receptor, hsCRP, and adverse cardiovascular outcomes was evaluated. Among 3406 participants with CAD, 479 had AHF. Participants with AHF were older; were less likely to be Black individuals; and had a lower body mass index, worse renal function, and a prior history of heart failure. In multivariable linear regression models adjusted for clinical and demographic confounders, participants with AHF had 15.6% higher soluble urokinase plasminogen activator receptor and 24.0% higher hsCRP levels. They were more likely to experience the following adverse outcomes: all‐cause death (adjusted hazard ratio [HR], 1.57 ([95% CI, 1.29–1.92]; P P =0.003). Mediation analysis showed that 47.0% (95% CI, 13.6%–81.2%]; P =0.006) of the indirect effect of AHF on cardiovascular death was mediated by circulating soluble urokinase plasminogen activator receptor levels. Conclusions: AHF is independently associated with immune activation, systemic inflammation, and adverse cardiovascular outcomes in patients with CAD. The association of AHF with adverse outcomes is partly mediated by immune activation, and targeting this pathway may help reduce the residual risk in patients with CAD.

Background: The survival benefit of revascularization of chronic total occlusion (CTO) of the coronary arteries remains a subject of controversy. We measured high sensitivity troponin‐I (hsTn‐I) levels as an estimate of myocardial ischemia in patients with stable coronary artery disease, with the hypothesis that (1) patients with CTO have higher levels of hsTn‐I than patients without CTO, (2) hsTn‐I levels will predict adverse cardiovascular events in patients with CTO, and (3) patients with elevated hsTn‐I levels will have a survival benefit from CTO revascularization. Methods and Results: In 428 patients with stable coronary artery disease and CTO undergoing coronary angiography, adverse event rates were investigated. Cox proportional hazards models and Fine and Gray subdistribution hazard models were performed to determine the association between hsTn‐I level and incident event rates in patients with CTO. HsTn‐I levels were higher in patients with compared with those without CTO (median 6.7 versus 5.6 ng/L, P =0.002). An elevated hsTn‐I level was associated with higher adverse event rates (adjusted all‐cause mortality hazard ratio, 1.19 [95% CI, 1.08–1.32]; P =0.030) for every doubling of hsTn‐I level. CTO revascularization was performed in 28.3% of patients. In patients with a high (>median) hsTn‐I level, CTO revascularization was associated with substantially lower all‐cause mortality (adjusted hazard ratio, 0.26 [95% CI, 0.08–0.88]; P =0.030) compared with those who did not undergo revascularization. In patients with a low ( < median) hsTn‐I level, event rates were similar in those with and without CTO revascularization. Conclusions: HsTn‐I levels may help identify individuals who benefit from CTO revascularization.